The third eldest in a family of twelve children, Segrelles exhibited artistic talent from a young age and began attending the Escuela de Bellas Artes de San Carlos at the age of nine. He continued his studies in Barcelona at the Provincial Academy of Fine Arts in 1904 and there he worked in the photography studio Napoleon where he began his career as an illustrator. Among other assignments, Segrelles produced some of the first comic books to be issued in Spain. His first published illustrations appeared as covers for love stories, then illustrated mystery novels and adventure tales. Illustrated editions of Faust, the Aeneid, the Illiad, Poe's Tales of Mystery and Imagination, The Divine Comedy, novels by Dickens, and biographies of Mozart, Goya, and Alexander the Great, soon followed. Between 1918 and 1922, Segrelles dedicated himself to a lavish edition of Don Quixote.
Segrelles' illustrations began to appear outside of Spain in The London Illustrated News following his award of the Gold Medal at the Barcelona International Exposition of 1929. His illustrations for Dante, Perrault, and Poe, as well as subjects inspired by the music of Wagner, Beethoven, and Chopin appeared in the Christmas issues of the British periodical and consequently gained the attention of the American publishing houses. His illustrations for H.G. Well's War of the Worlds which appeared in the pages of The Sketch also served to catapult the artist's international acclaim. Segrelles went on to work for American Weekly, Redbook, Fortune, and Cosmopolitan magazines as well as the American motor companies Ford, Packard, and Lincoln.
Remaining all but forgotten outside of his native Spain, Segrelles was once widely regarded as the finest Spanish illustrator of his generation and an imaginative painter of exceptional brilliance. While comparisons with the work of Gustave Doré, Arthur Rackham, Edmund Dulac, and the American illustrator Maxfield Parrish were once unavoidable, Segrelles' visions had unique and persuasive qualities that captivated audiences with unorthodox perspectives and theatrical lighting effects, giving his work a heightened mood of eeriness and unreality unmatched by his contemporaries. Although he was barely known in the United States in the 1960s, he was appreciated by Roy Krenkel, who shared this work with Frank Frazetta, leading to the obvious influence of Segrelles’ work on Frazetta’s own paintings.